Penis & scrotum

Dysplasia / carcinoma in situ

Extramammary Paget disease


Editorial Board Member: Bonnie Choy, M.D.
Deputy Editor-in-Chief: Maria Tretiakova, M.D., Ph.D.
Roberto Gonzalez, B.S.
Debra L. Zynger, M.D.

Last author update: 14 March 2022
Last staff update: 13 October 2022

Copyright: 2002-2022, PathologyOutlines.com, Inc.

PubMed Search: Paget disease of penis scrotum

Roberto Gonzalez, B.S.
Debra L. Zynger, M.D.
Page views in 2021: 1,779
Page views in 2022 to date: 2,789
Cite this page: Gonzalez R, Zynger DL. Extramammary Paget disease. PathologyOutlines.com website. https://www.pathologyoutlines.com/topic/penscrotumpenilepagets.html. Accessed December 9th, 2022.
Definition / general
  • Paget disease of the penis and scrotum is a rare, intraepidermal adenocarcinoma; it arises as a primary tumor or from secondary involvement of a nonpenoscrotal neoplasm
Essential features
  • Single or clusters of atypical intraepithelial cells involving penis or scrotum
  • Primary tumor expresses CK7 and is negative for CK20 and melanocytic markers
  • Correlation with clinical history for evaluation of possible secondary malignancies
Terminology
  • Paget's disease, extramammary Paget disease, extramammary Paget's disease
ICD coding
  • ICD-O: 8542/3 - Paget disease, extramammary (except Paget disease of bone)
Epidemiology
  • Limited data on population incidence
  • Surveillance, Epidemiology and End Results (SEER) registry reported 61% Caucasian and 36% Asian or Native American (Dis Colon Rectum 2019;62:1283)
Sites
  • Penis or scrotum epidermis or dermis
Pathophysiology
Etiology
Clinical features
Diagnosis
Laboratory
  • Evaluate tumor serum markers such as CEA and PSA
Radiology description
  • Ultrasound may show skin lesion with irregular contours, heterogenous echogenicity, increased vascularity and dermal invasion (Ultrasound Q 2020;36:84)
  • Imaging may be used to assess for nonscrotal primary tumors and to rule out distant metastases
Radiology images

Images hosted on other servers:

Scrotal MR and ultrasound

Scrotal ultrasound

Prognostic factors
Case reports
Treatment
  • Wide local excision or Mohs micrographic surgery
  • If surgery is not possible, alternative therapies (with limited data supporting their use) include imiquimod cream, photodynamic therapy, radiotherapy and chemotherapy (Dermatol Online J 2019;25:13030)
Clinical images

AFIP images

Scrotal lesion



Images hosted on other servers:

Erythematous penile patches

Gross description
Gross images

Contributed by Debra L. Zynger, M.D.
White lesion White lesion

White lesion

Frozen section description
Frozen section images

Contributed by Debra L. Zynger, M.D.
Extensive infiltrate

Extensive infiltrate

Numerous large cells

Numerous large cells

Rare large cells

Rare large cells

Deceptive tumor

Deceptive tumor

Microscopic (histologic) description
Microscopic (histologic) images

Contributed by Debra L. Zynger, M.D.
Intraepithelial growth

Intraepithelial growth

Nests and single cells

Nests and single cells

Basal location

Basal location

Nuclear features

Nuclear features

Microinvasion Microinvasion

Microinvasion


H&E for IHC

H&E for IHC

CK7

CK7

GATA3

GATA3

CK5/6

CK5/6

p63

p63

S100

S100

Virtual slides

Images hosted on other servers:

Invasion

Electron microscopy description
Molecular / cytogenetics description
Sample pathology report
  • Penis and scrotum, wide local excision:
    • Extramammary Paget disease with focal microinvasion (see comment)
    • Tumor involves margins in blocks A1 (12 - 3:00 penile margin shave), A3 (3 - 6:00 penile margin shave) and A4 (9 - 12:00 penile margin shave); all other resection margins are negative for tumor
    • Comment: Tumor cells are positive for CK7 and GATA3 and are negative for CK5/6, p63, CK20, CDX2 and S100.
Differential diagnosis
  • Melanoma in situ:
    • No keratinocyte layer in between tumor cells and dermis
    • Both can have intracellular melanin pigment
    • Positive: S100, HMB45, MelanA
    • Negative: AE1 / AE3, CK7
  • Squamous cell carcinoma in situ / penile intraepithelial neoplasia (PeIN):
    • Will not have exclusively pagetoid growth; will see full layers of atypical cells
    • Cells have eosinophilic rather than pale cytoplasm
    • May see intraepithelial bridges
    • Positive: p63
    • Negative: CEA
  • Mucinous metaplasia:
    • Bland cells intraepidermal cells containing mucin
  • Pagetoid dyskeratosis:
    • Most common in head and neck
    • Usually incidental finding
    • Has been reported in foreskin
    • Also has enlarged cells with pale cytoplasm
    • Found in the upper layers of the squamous epithelium rather than basal predominant
    • Has nuclear halo / clearing
    • Pyknotic, bland nuclei
  • Clear cell papulosis:
    • Usually occurs in Asian children
    • Numerous small lesions
    • Cells large with pale cytoplasm but lack aggressive nuclear features like nuclear pleomorphism or prominent nucleoli
    • Similar staining profile
  • Secondary versus primary extramammary Paget disease:
    • Clinical history and presentation critical
    • See positive and negative stain sections above
Board review style question #1

A 68 year old man presented with a whitish, itchy plaque-like lesion that was located at the base of his penis and had grown larger over the past 2 years. The lesion was resected and a microscopic photo is shown above. Immunostains reveal that the lesional cells are positive for AE1 / AE3, CK7 and CEA and are negative for S100, CK20, CK5/6, p63 and NKX3.1. What is the diagnosis?

  1. Malignant melanoma
  2. Primary extramammary Paget disease
  3. Prostatic adenocarcinoma
  4. Squamous cell carcinoma
  5. Urothelial carcinoma
Board review style answer #1
B. Primary extramammary Paget disease. Penoscrotal extramammary Paget disease presents in elderly men as a whitish plaque. The lesion is often misdiagnosed for several years as a nonneoplastic lesion. Primary penoscrotal extramammary Paget disease tumoral cells express AE1 / AE3, CK7 and CEA and are negative for S100, CK20, CK5/6 and NKX3.1. Melanoma is positive for S100 and negative for AE1 / AE3. Prostatic adenocarcinoma is negative for CK7 and positive for NKX3.1. Squamous cell carcinoma is negative for CEA and positive for p63 and CK5/6. Urothelial carcinoma is positive for p63. Of note, primary penoscrotal extramammary Paget disease expresses GATA3 and AR, overlapping with urothelial carcinoma and prostatic adenocarcinoma.

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Reference: Extramammary Paget disease
Board review style question #2

Which of the following markers is typically expressed in penoscrotal primary extramammary Paget disease?

  1. CK5/6
  2. CK7
  3. CK20
  4. p63
  5. S100
Board review style answer #2
B. CK7 (shown in the image). Most cases of primary extramammary Paget disease express AE1 / AE3, EMA, CK7, CEA, GATA3 and AR. There is variable expression of GCDFP and HER2. Most cases are negative for CK20, CDX2, S100, HMB45, p63, CK5/6, PSA and prostein.

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Reference: Extramammary Paget disease
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